Juvenile diabetes mellitus or insulin dependent diabetes mellitus outranks all endocrine disorders in incidence, morbidity and mortality. The risk of its complications and mortality does not appear to have changed in the last 30 years. The cause of the disease is still unknown, but genetic predisposition, viruses and autoimmune activity of the hosts all appear to be important. Recently, we have used cultured human insulinoma cells as model pancreatic islet cells to demonstrate the presence of antibody and sensitized lymphocytes to insulinoma cells in patients. This proposal is designed to further enlarge our finding to additional patients. Also, a new assay has been developed to test cell mediated immunity of patients against implicated viruses. An animal model is expected to develop to test all those factors which led to the pathogenesis of the disease. These information will provide a better understanding of the disease as well as preventive measures in the future.